Our recent studies indicate that implants of normal fetal preoptic (POA) brain tissue into the third ventricle of the female hypogonadal mouse, genetically deficient in hypothalamic gonadotropin releasing hormone (GnRH), reversed the hypogonadism. Immunocytochemistry revealed that the brain grafts contain GnRH-cells and that processes extend from the graft into the host median eminence. Pituitary and plasma levels of LH and FSH rose and the gonads developed. The females entered constant vaginal estrus and when mated, ovulated (apparently reflexively) and maintained normal pregnancies. These findings demonstrate that the grafted tissue is capable of physiological response. The present studies are designed to further define some of the factors involved in the regulation of the GnRH containing implant. LH release in the host animal will be determined in response to the sensory stimulus of coitus, and to the hormonal challenge of estrogen and progesterone administration. Neuronal regulation of the transplants will be studied with the use of retrograde axonal transport techniques, with the aim of demonstrating whether certain aferent pathways are necessary for the transplant to support ovulation. In addition, studies will evaluate the usefulness of the POA implants in remedying the reproductive deficiencies of the neonatally androgenized rat. Methods used will include stereotaxic surgery, behavioral studies, neuroanatomical tracing, radioimmunoassay of gonadotropins in both plasma and pituitary, and light microscopic analysis of ovarian development. New information from these studies will provide greater understanding of the way in which a brain tissue graft interacts with the host both functionally and anatomically.